1. Field of the Invention
The invention relates to methods for treating cell culture media for use in a bioreactor using ultraviolet C (UVC) light and filtration.
2. Background of the Invention
Viral contamination of cellular media and supernatants poses a large challenge to biopharmaceutical manufacturers worldwide. Several methods have been employed to inactivate and/or remove large or small, enveloped or non-enveloped (or “naked”) DNA or RNA viral particles from cellular supernatants. Examples of these approaches include 20 nm filtration technology, Q membrane chromatography, and depth filter technology. These methods, however, have been used primarily as a means for viral inactivation (i.e., viral clearance) of media and supernatants collected from cell lines or tissues (i.e., downstream of protein production).
Such viral clearance methods have not been used to treat cell culture media prior to exposure to cell lines or tissues (i.e., upstream of protein production) for several reasons. First, employing such techniques to the treatment of large-scale cellular media, where up to 20,000 L of cellular media is processed per day, can be prohibitive in terms of time and cost. Second, such methods have historically been employed to remove contaminants from large-scale cellular supernatants as a preliminary step in the purification of therapeutic protein products from the large-scale cellular supernatants prior to administration of the therapeutic protein products to patients. Third, there has been no required or documented need in the art for the inactivation or removal of viral particles in the upstream process of protein production. Finally, bioreactors and fermenters are frequently not equipped with the machinery required to carry out these techniques, and the cost of retrofitting exisiting equipment to add such machinery can be exorbitantly high.
In addition to the above techniques, ultraviolet light has been used to treat large-scale protein preparations prior to the purification of these proteins from cellular supernatants. However, as with other methods of treating large-scale cellular supernatants prior to the purification and isolation of therapeutic protein products from the cellular supernatants, ultraviolet light exposure has been used primarily downstream of protein production. In other words, no prior art methods exist in which ultraviolet light (alone or in combination with other purification or treatment methods) has been used to treat cell culture media prior to introducing the cell culture media into a bioreactor. Thus, there is a need in the art for methods for treating cell culture media for use in a bioreactor. Such methods would be particularly useful for protecting valuable cell lines from viral contamination, saving costs lost as a result of contaminated and unusable media, and increasing the efficiency of protein production by such cell lines. Therefore, the development of such methods would have wide application in the manufacture of biopharmaceuticals.